Dong Z, Qi X, Xie K, Fidler I J
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Immunol. 1993 Sep 1;151(5):2717-24.
We investigated tumoricidal activation and induction of nitric oxide synthase (NOS) activity in macrophages from LPS-responsive (C3H/HeN) and -unresponsive mice (C3H/HeJ). Macrophages were incubated in vitro with a synthetic lipopeptide or with LPS and IFN-gamma. LPS and IFN-gamma activated C3H/HeN but not C3H/HeJ macrophages to lyse B16 melanoma cells. In contrast, lipopeptide and IFN-gamma activated macrophages from both strains of mice. Genistein, a specific inhibitor of protein tyrosine kinase, significantly blocked tumoricidal activation of macrophages from both strains of mice. Genistein did not affect tumor cell binding but significantly inhibited the production of nitric oxide. Genistein, herbimycin A, and tyrphostin inhibited the induction of NOS activity in macrophages from both strains of mice. These data suggest that protein tyrosine kinase activity is involved in the signal transduction pathway of LPS and other synthetic bacterial-related immunomodulators at a point preceding triggering of macrophage tumoricidal activation and expression of inducible NOS activity.
我们研究了来自对脂多糖（LPS）有反应的（C3H/HeN）和无反应的小鼠（C3H/HeJ）的巨噬细胞中的杀肿瘤激活作用以及一氧化氮合酶（NOS）活性的诱导情况。巨噬细胞在体外与合成脂肽或与LPS和γ干扰素一起孵育。LPS和γ干扰素激活C3H/HeN巨噬细胞使其裂解B16黑色素瘤细胞，但不激活C3H/HeJ巨噬细胞。相反，脂肽和γ干扰素激活了两种小鼠品系的巨噬细胞。染料木黄酮，一种蛋白酪氨酸激酶的特异性抑制剂，显著阻断了两种小鼠品系巨噬细胞的杀肿瘤激活作用。染料木黄酮不影响肿瘤细胞的结合，但显著抑制一氧化氮的产生。染料木黄酮、除莠霉素A和 tyrphostin抑制了两种小鼠品系巨噬细胞中NOS活性的诱导。这些数据表明，蛋白酪氨酸激酶活性在巨噬细胞杀肿瘤激活作用触发和诱导型NOS活性表达之前的某个点参与了LPS和其他合成细菌相关免疫调节剂的信号转导途径。
